BIOCHEMICAL MARKERS IN PREDICTING PREECLAMPSIA IN LATE FIRST TRIMESTER AND EARLY SECOND TRIMESTER OF
PREGNANCY”
Dissertation submitted to
The Tamil Nadu Dr. M.G.R Medical University
In partial fulfillment of the requirement for the award of the Degree of M.S. OBSTETRICS AND GYNAECOLOGY
BRANCH II
THE TAMIL NADU Dr. M.G.R MEDICAL UNIVERSITY INSTITUTE OF OBSTETRICS AND GYNAECOLOGY, GOVERNMENT HOSPITAL FOR WOMEN & CHILDREN,
MADRAS MEDICAL COLLEGE.
APRIL-2018
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BONAFIDE CERTIFICATE
This is to certify that this dissertation entitled “FETAL HEMOGLOBIN AND ALPHA 1 MICROGLOBULIN AS BIOCHEMICAL MARKERS IN PREDICTING PREECLAMPSIA IN LATE FIRST TRIMESTER AND EARLY SECOND TRIMESTER OF
PREGNANCY” is the bonafide original work done by Dr.I.INBA PRIYANKA, post graduate in the Department of Obstetrics
and Gynaecology, under the guidance of Dr.S.VIJAYA, MD, DGO., Professor, Institute of Social Obstetrics and Gynaecology, Kasturba Gandhi Hospital, Madras Medical College, Chennai, towards partial fulfilment of the requirement of the Tamil Nadu Dr. M.G.R Medical University for the award of M.S Degree in Obstetrics and Gynaecology,
April 2018. The period of post graduate study is from June 2015 to June 2018.
GUIDE DIRECTOR
Prof.Dr.S.VIJAYA , MD, DGO Prof. Dr.T.K.SHAANTHY GUNASINGH MD, DGO Professor, Director and Superindent,
ISO-KGH IOG
Prof R. NARAYANABABU, MD, DCH Dean,
Madras Medical College.
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DECLARATION
I solemnly declare that this dissertation “FETAL HEMOGLOBIN AND ALPHA 1 MICROGLOBULIN AS BIOCHEMICAL MARKERS IN PREDICTING PREECLAMPSIA IN LATE FIRST TRIMESTER AND EARLY SECOND TRIMESTER OF PREGNANCY” was prepared by me under the guidance and supervision of Dr.S.VIJAYA, MD, DGO., Professor, Institute of Social Obstetrics and Gynaecology, Kasturba Gandhi Hospital, Madras Medical College, Triplicane, Chennai.
This dissertation is submitted to The Tamil Nadu Dr. M.G.R. Medical University, Chennai in partial fulfillment of the University regulations for the award of the degree of M.S. (Obstetrics and Gynaecology).
Place: Chennai
Date: DR.I.INBA PRIYANKA
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ACKNOWLEDGEMENT
I gratefully acknowledge and sincerely thank Dr.R.Narayana Babu, MD, DCH., Dean, Madras Medical College, for allowing me to use the
facilities and clinical materials available in the hospital.
I extend my sincere thanks and gratitude to Dr.T.K.Shaanthy Gunasingh, MD, DGO., Director and Superintendent, IOG, for granting me permission to utilize the facilities of the institute for my study.
I am extremely grateful to our beloved Professor, Dr.S. VIJAYA, MD, DGO., Professor of Obstetrics & Gynaecology, ISO-KGH, for her valuable guidance, motivation and encouragement given during the study.
I humbly thank all the Professors and Assistant Professors of IOG, Egmore and Government Kasturba Gandhi Hospital, Triplicane for all their help during the course of the study.
My sincere thanks to my statistician Mr.ASHOK, who patiently helped me in analysing the results of this study.
My special thanks to my brother Dr.I.INBA PRAVEEN, my parents and friends for their physical help and moral support without which nothing would have been possible.
I am immensely grateful to all the patients who took part in the study.
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CERTIFICATE
This is to certify that this dissertation work titled
“FETAL HEMOGLOBIN AND ALPHA 1 MICROGLOBULIN AS BIOCHEMICAL MARKERS IN PREDICTING
PREECLAMPSIA IN LATE FIRST TRIMESTER AND EARLY SECOND TRIMESTER OF PREGNANCY” of the candidate
Dr. I. INBA PRIYANKA, M.B.B.S., with Registration Number:
221516007 for the award of MS Branch-II, in Obstetrics &
Gynaecology. I personally verified the urkund.com website for the
purpose of plagiarism Check. I found that the upload thesis file contains from introduction to conclusion pages and result shows 2% (Two percentage) of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
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TABLE OF CONTENTS
SL.NO CONTENTS PAGE NO
1 INTRODUCTION 1
2 AIM OF THE STUDY 3
3 REVIEW OF LITERATURE 5
4 MATERIALS AND METHODS 32
5 OBSERVATION AND RESULTS 37
6 DISCUSSION 69
7 LIMITATION 74
8 SUMMARY 76
9 CONCLUSION 79
10 BIBLIOGRAPHY 81
11 PROFORMA 92
12 INFORMED CONSENT FORM 96
13 MASTER CHART 100
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INTRODUCTION
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Preeclampsia is a systemic syndrome manifesting as “new onset hypertension and proteinuria after 20 weeks of gestation” occurring in about 3 to 5% of pregnant women Preeclampsia is a complex clinical syndrome with hypertension representing as the major manifestation.
Pathogenesis of preeclampsia include defective perfusion of maternal spiral arteries by the trophoblast, endothelial injury leading to activation of coagulation, secretion of endothelial cell toxin, altered endothelial permeability and impairment of vasodepressor function. These changes lead to the clinical manifestation of preeclampsia. The primary biochemical, immunologic and genetic basis of preeclampsia remains speculative.
However recent studies here indicated the involvement of hemoglobin induced oxidative stress in the development of preeclampsia.
The oxidative stress may damage the blood placenta barrier leading to elevated levels of HbF in maternal plasma or serum. In addition, marker for oxidative stress such as antioxidant endogenous protein α1 microglobulin were found to be elevated.
In this background the present study is undertaken to assess the levels of fetal hemoglobin and α1 microglobulin in late first and early second trimester and to determine whether they can be used as predictive markers for preeclampsia.
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AIMS AND
OBJECTIVES
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To establish association between high levels of fetal hemoglobin and alpha 1 microglobulin in plasma of pregnant womenin 10 to 16 weeks of gestational age and subsequent development of preeclampsia.
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REVIEW OF
LITERATURE
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Hypertensive disorders are one of the most common medical disorders of pregnancy. It has an incidence between 5 to 10%.
About 20% of fetal deaths and 30% of maternal death are due to hypertensive disorders of pregnancy. The major focus of research in obstetrics is to identify mothers who are at risk of adverse pregnancy outcome.
EPIDEMIOLOGY AND RISK FACTORS
Hypertensive disorders complicate nearly 7.5% of nulliparous women. Even though preeclampsia occurs mainly in the nulliparous women, there is increased risk of preeclampsia in multiparous women with a new partner which is similar to that of nulliparous women.
Increased interpregnancy interval and change in paternity may increase the risk of developing preeclampsia. Increased incidence is also due to postponement of first pregnancy to a later age and increased prepregnancy weight.
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A women who has developed preeclampsia is at increased risk of developing the same in subsequent pregnancies. Diabetes, renal diseases, chronic hypertension, hypercoagulable states are some disorders that increase the risk of preeclampsia. Multifetal pregnancy and hydatiform mole have large placental mass and increase the chance of preeclampsia.
Smoking provides protection against development of preeclampsia.
DEFINITION
Hypertension is defined as systolic blood pressure equal to or greater than 140 mmof Hg and / or diastolic blood pressure of 90mm of Hg or more measured on two occasions at least 4 hours apart within 7 days beyond 20 weeks of gestation.
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National high blood pressure education programme (2000) categorized hypertensive disorders in pregnancy as follows
1. Gestational hypertension 2. Preeclampsia
3. Eclampsia
4. Chronic hypertension
5. Superimposed preeclampsia on chronic hypertension
GESTATIONAL HYPERTENSION
Gestational hypertension is diagnosed in a pregnant women when the blood pressure is 140/90 mm of Hg or greater after 20 weeks of gestation which returns back to normal by 12 weeks postpartum without proteinuria.
Chronic hypertension is diagnosed, if blood pressure remains elevated beyond 12 weeks postpartum. When gestational hypertension develops before 35 weeks of gestation, there is increased chance of patient developing preeclampsia.
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PREECLAMPSIA
Preeclampsia is defined as “ onset of hypertension after twentieth week of gestation, along with proteinuria. Proteinuria is confirmed if there is > 300mg of protein in 24 hours urine collection or a urinary dipstick shows >= +2 or protein/ creatinine ratio more than 0.3.
Preeclampsia complicates 2 to 8% of pregnancies. ACOG removed proteinuria as a criteria for diagnosing preeclampsia in 2013. When preeclampsia develops before 34 weeks but after 20 weeks of gestation, it is called early onset preeclampsia.
Preeclampsia is diagnosed in the absence of proteinuria when the patient develops any one of the following along with new onset hypertension
1. Platelets < 1,00,000/mm3
2. Elevated aspartate transaminase or alanine
transaminase atleast twice normal concentrations 3. Serum creatinine > 1.1 mg/dl
4. Microangiopathic hemolysis
5. Persistent headache or other cerebral or visual disturbances
6. Persistent epigastric pain / right upper quadrant pain
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Severe preeclampsia is termed when blood pressure is
> 160/110mm of hg with signs and symptoms of end organ damage.
ECLAMPSIA
Convulsions that cannot be attributed to other causes and/ or unexplained coma during pregnancy or puerperium ina woman with preeclampsia.
CHRONIC HYPERTENSION
Hypertension diagnosed before 20 weeks of gestational age or after 20 weeks of gestation and persistent beyond 12 weeks postpartum or whichever is diagnosed before pregnancy.
SUPERIMPOSED PREECLAMPSIA ON CHRONIC HYPERTENSION
A sudden increase in blood pressure, proteinuria or < 1 lakh platelet count in hypertensive women and proteinuria before 20 weeks gestation or a new onset proteinuria in hypertensive women after 20 weeks of gestation age.
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IMPENDING ECLAMPSIA
The following are the signs and symptoms of impending eclampsia -Persistent headache
-Visual disturbances -Oliguria
-Nausea/vomiting -Epigastric pain
-Restlessness/agitation -Coagulatory disturbances
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CLINICAL FEATURES
Preeclampsia is a condition which is difficult to diagnose due to its variety of presentations and lack of a specific diagnostic test.
Preeclampsia is diagnosed when a pregnant women develops hypertension( systolic blood pressure >=140 mm of Hg or diastolic blood pressure >=90mm of Hg ) and proteinuria ( 300mg or greater in 24 hr urine sample) after 20 weeks of gestation.
About 20% of women with atypical preeclampsia have minimal or no proteinuria.
Previously preeclampsia is characterised by hypertension, proteinuria, and oedema. However oedema isno longer considered for diagnosis. Currently preeclampsia is divided into mild and severe preeclampsia. Headache, blurring of vision, epigastric/right upper quadrant pain, oliguria, hemolysis, pulmonary oedema, platelet count<1,00,000mm3 are signs of severe preeclampsia.
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HELLP syndrome include hemolysis, elevated liver enzymes and low platelet count. It is a severe form of the disease and indicate immediate delivery.
Fetal complications caused by preeclampsia include oligohydramnios, IUGR, iatrogenic prematurity and perinatal death.
Eclampsia develops in 2% of women with preeclampsia. Eclamptic seizures is more common in immediate postnatal period. But seizures can also occur from 48 hours postpartum to one month postpartum. Nearly one third patients with postpartum eclamptic seizures have never shown any signs of preeclampsia during pregnancy.
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LONG TERM MATERNAL COMPLICATIONS
It has been believed that with the delivery of the placenta, complication of preeclampsia resolve. But new research suggests that risk to the mother persists long after her reproductive years are over. The risk of cardiovascular and cerebrovascular is doubled in woman with preeclampsia and gestational hypertension. 20% of preeclamptic women develop hypertension within 7 years of pregnancy.
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PATHOGENESIS
The pathophysiology of preeclampsia starts from the placenta.
Preeclampsia is described as a two stage syndrome.
GENETIC FACTORS
ENVIRONMENTAL FACTORS
IMMUNOLOGICAL FACTORS
IMPAIRED PLACENTAL IMPLANTATION
PLACENTAL ISCHEMIA( PRODUCTION OF SFLT1 & OTHER PLACENTAL FACTORS
MATERNAL ENDOTHELIAL DYSFUNCTION DECREASED PLACENTAL BLOOD FLOW
MATERNAL SYMPTOMS (eg. Hypertension) STAGE
ONE
STAGE TWO
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Newer techniques like proteomics and genomics have revealed fetal HbF as a potential factor linking stage 1 and 2 in preeclampsia. The analyses have revealed an accumulation of fetalHbF in placental vascular lumen. The cells which express HbF have identified as hematopoietic stem cells located close to lumen.
Cell free hemoglobin and its metabolites are toxic to tissue since they cause oxidative stress which is an imbalance between reactive oxidative compounds and physiological antioxidative defence mechanisms. Antioxidants inhibit oxidation. Alpha 1 microglobulin is a protein which has both enzymatic and non enzymatic antioxidant properties.
In preeclampsia, oxidative stress occurs in both placenta and maternal circulation. Extracellular Hb induces oxidative stress at a very high level. The cell Hb binds to nitric oxide and causes vasoconstriction which leads to increased blood pressure.
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In order to protect the body against harmful effects of free Hb, a range of physiological defence mechanisms have evolved. Cell free Hb is bound to haptogloblin while Hb metabolite heme to hemopexin, albumin, alpha 1 microglobulin.
Alpha 1 microglobulin is a plasma protein that provides protection due to its ability to bind and neutralize free heme and radicals. Several studies have shown that there is upregulation of A1M expression in liver and placenta following exposure to Hb. The serum concentration of A1M have been shown to be significantly elevated in maternal blood in first trimester for pregnant women subsequently developing, preeclampsia.
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Modified two stage model on basis of HbF hypothesis
SHALLOW INVASION OF MATERNAL SPIRAL ARTERIES
CELL FREE FETAL Hb LEAKAGE INTO MATERNAL CIRCULATION
MATERNAL HYPERTENSION PROTEINURIA
OXIDATIVE STRESS
UPREGULATION OF ANTIOXIDANTS INCREASED PLACENTAL SYNTHESIS OF
FETAL Hb
DECREASED BLOOD FLOW TO PLACENTA
ENDOTHELIOSIS IN MATERNAL VESSELS AND GLOMERULUS STAGE
ONE
STAGE TWO
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PATHOPHYSIOLOGY
ABNORMAL PLACENTATION
In normal pregnancy, there is controlled trophoblastic invasion from the decidua up to the inner third of the myometrium thus the endothelial and muscular layer of spiral arteries are disrupted converting the small muscular arteries to large capacity low resistance vascular spaces a process called pseudovascularization. It occurs in 2 stages. First occurs before 12 weeks of GA upto the interface between decidua and myometrium. Second stageoccurs between 12 & 16 weeks and invades spiral arteries in the intramyometrial segment.
In preeclampsia, there is decreased or absent second wave of trophoblastic invasion of maternal spiral arteries as compared to normal pregnancy.
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MATERNAL ENDOTHELIAL DYSFUNCTION
Placenta is the organ of origin in preeclampsia. However, maternal endothelium is the organ of target. The released vasopressive factors from placenta cause damage to endothelium of maternal organs. In normal pregnancy, decrease in blood pressure and vascular resistance occurs. In preeclampsia, systemic vascular resistance is high & cardiac output is low due to generalized vasoconstriction
.
PRO AND ANTI-ANGIOGENIC FACTORS
The vascular development in placenta involves several pro and anti angiogenic factors .They include
VEGF (Vascular Endothelial Growth Factor )
PGF (Placental Growth Factor )
SFLt-1 (Soluble fms like tyrosine kinase – 1)
Soluble endoglin
Imbalance in these factors may result in endothelial dysfunction.
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RENIN ANGIOTENSIN ALDOSTERONE SYSTEM
Pregnant women usually have response to the effects of Angiotensin II. In patients with preeclampsia aldosterone level is increased in 3rd trimester. In addition the refractoriness to angiotensin II is also lost in the second trimester, This is because in normal pregnancy there is down regulation of angiotensin receptors. But in preeclamptic women, there is elevated levels of angiotensin receptors.
OXIDATIVE STRESS
In the preeclamptic women there is an increase in serum lipid peroxide levels which causes cellular damage. The oxidative stress causes increase in capillary permeability leading to oedema, proteinuria and microvascular coagulation .
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HEMATOLOGICAL CHANGES
Due to endothelial damage there is leakage of plasma into interstitial space causing decreased blood volume. These patients have thrombocytopenia, hemolysis and deranged coagulation profile depending on the severity of the disease.
CARDIOVASCULAR CHANGES
There is increased peripheral resistance and decreased cardiac output. Pulmonary wedge pressure and central venous pressure are reduced in preeclampsia.
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HEPATIC CHANGES
Hepatic changes include hemorrhage, peripheral fibrin deposition, areas of infarction and necrosis. The subscapular hemorrhages which occurs in liver gives it a mottled appearance. The subcapsular hemorrhage causes right upper or epigastricpain .
RENAL CHANGES
In the pre eclamptic women, changes like glomerular enlargement, focal segmental glomerular sclerosis, swelling of mesangium, endothelial cell hyperplasia, sub endothelial fibrinoid deposition occur. Glomerular filtration rate and renal plasma flow are reduced in pre eclampsia.
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CHANGES IN BRAIN
The most common finding in brain is oedema due to both increased vasospasm of cerebral arterioles and over dilatation of vessels due to failure of autoregulatory mechanism of brain. Changes are most commonly seen in posterior hemisphere causing visual disturbances like scotoma, blurring of vision and diplopia .
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MATERNAL COMPLICATIONS - Eclampsia
-HELLP (Hemolysis, Elevated Liver enzymes, Low platelets) -Pulmonary edema
-Disseminated Intravascular coagulopathy -Hypertensive Encephalopathy
-Acute renal failure
FETAL COMPLICATIONS
Intrauterine fetal growth restriction
Preterm birth
Oligohydramnios
Intrauterine death
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HELLP SYNDROME
The term „HELLP‟ was coined by Weinstein in 1982 . H – Hemolysis
EL – Elevated liver Enzymes LP – low platelets
Hemolysis is defined as presence of abnormal peripheral smear with schistocytes, total bilirubin level more than 1.2 mg/dl, liver enzymes are elevated when aspartate aminotransferase is more than 70U/L and LDH more than 600 U/L .When platelets are less than 1,00,000/ mm3 it is called low platelet count.
Martin el al categorized HELLP Syndrome into three classes based on platelet count (Mississipi scoring ). Class 1 is defined as platelet count less than 50,000/mm3. Class 2 as platelet count less than 50,000 to 1,00,000/mm3 and class 3 as platelet count more than 1,00,000/mm3.
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MANAGEMENT
The only definitive treatment of preeclampsia is termination of pregnancy.
Management depends on the severity of the disease and the period of gestation.
Elective induction of labour is done when the gestational age is 37 weeks or more.
In severe pre eclampsia,34 weeks is taken as the cut off for termination of pregnancy.
However when severe preeclampsia is not responding to treatment, termination of pregnancy is offered after a course of steroids, before 34 weeks.
MANAGEMENT OF SEVERE PREECLAMPSIA ACCORDING TO GESTATIONAL AGE
<24 weeks – Stabilise the patient and terminate
25-33 weeks-Expectant management and maternal and fetal monitoring, steroids given for lung maturity of fetus.If there is maternal or fetal indication then terminate the pregnancy.
>34 weeks-Stabilise the patient with fetal monitoring and then deliver.
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ANTIHYPERTENSIVE THERAPY
The blood pressure at which antihypertensive should be started is still controversial.Antihypertensive should be started in case of severe hypertension (ie) diastolic pressure >110 mm of Hg and / or systolic pressure >160 mm of Hg to prevent maternal and fetal complications.
Recent guidelines indicate antihypertensive treatment for mild
preeclampsia(140-159/90-109 mm of Hg) to maintain systolic BP at 130-155 and diastolic BP at 80-105 mm of Hg.
First line drugs for antihypertensive therapy are labetolol, nifedipine and alpha methyl dopa.
Reducing maternal BP does not have effect on fetus, but may reduce fetal perfusion and may indirectly affect the fetal growth.
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LABETOLOL
It is an alpha and beta blocker. Used as first line therapy in pregnancy oral drug given as 100-400 mg twice daily.
For severe preeclampsia iv dose of 10-20 mg given initially
followed by 20-80 mg every 30 minutes upto a maximum dose of 300 mg
ALPHA METHYL DOPA
It is a centrally acting alpha adrenergic agonist.It decreases the sympathetic tone and arterial blood pressure.
It is given as a dose of 250-500 mg orally two to three times a day upto a maximum dose of 2 g.
NIFEDIPINE
It is a calcium channel blocker. It is given as a dose of 10-20 mg three to four times daily with a maximum dose of 120 mg/day.
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ECLAMPSIA MANAGEMENT
The management of eclampsia includes
1) Clearing airways
2) Control of seizures (MgSO4 regimen) 3) Control of BP
4) Delivery of baby
5) Postpartum monitoring
MgSO4 REGIMEN (ZUSPAN REGIMEN is followed in my Institution)
Loading dose: 4 g of 20% MgSO4 given over 15 – 20 minutes
Maintenance dose: 1g/hr of MgSO4 is infused. It is discontinued after 24 hours of delivery or last convulsions whichever is last.
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CONTRACEPTION
Postpartum IUCD may be inserted in preeclamptic women.
Progesterone only pills may be prescribed at 6 weeks postpartum when BP is found to be normal.
When BP remains elevated, followup at 12 weeks postpartum required and women may be offered IUCD or condoms.
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MATERIALS AND
METHODS
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The present study was undertaken in the Department of Obstetrics and Gynaecology, between September 2016 and august 2017. This was a prospective cohort study done to establish association between high levels of fetal hemoglobin and alpha 1 microglobulin in pregnant women of 10 to 16 weeks of GA and subsequent development of preeclampsia in these women.A total of 100 pregnant women were included in the study.
INCLUSION CRITERIA:
-10 – 16 weeks of pregnancy -Singleton /Multiple pregnancy -Age 20-35 years
-Both primi and multigravida -BMI 16-35
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EXCLUSION CRITERIA -Diabetes -Hypertension -Renal disease -Epilepsy
-Vascular disorders
PARAMETERS STUDIED:
-Fetal hemoglobin -Alpha 1 microglobulin
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PROCEDURE:
Hundred pregnant women attending IOG hospital who were willing to participate in the study were recruited after getting consent.
Blood samples of these women were collected and measured using ELISA. They were managed by department protocol and followed till delivery. General parameters like age, parity, BP, BMI, gestational age, mode of delivery and perinatal outcome were compared between both groups. The values of fetal hemoglobin and α1 microglobulin were correlated with the development of preeclampsia.
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STATISTICAL ANALYSIS:
Data were collected and included in a data based system and analysed by statistician. Parametric data were expressed as mean and standard deviation. It was analysed statistically using t-test and non parametric data were expressed as percentages and analyzed using chi square. Receiver operator characteristics analysis was used to identify the optimal threshold values of fetal hemoglobin and α1 microglobulin
.
Sensitivity, specificity, positive and negative predictive values of fetal hemoglobin and alpha 1 microglobulin were profiled by curves. All participants were subjected to full history taking and clinical examination.
Fetal hemoglobin and alpha 1 microglobulin levels were measured by ELIZA technique.
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RESULTS
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The present study was conducted in the department of Obstetrics and Gynaecology, from September 2016 to August 2017. One hundred women constituted the study group. Levels of fetal hemoglobin and α1 microglobulin were estimated. The results are presented below.
Frequency Table: TABLE I
Age group Frequency Percent
21-24 Years 24 24.0
25-28 Years 61 61.0
29-32 Years 15 15.0
Total 100 100.0
FIGURE I
In my study there were 24% women between 21-24 years,61% women between 25-28 years and 15% women between 29-32 years.
0%
10%
20%
30%
40%
50%
60%
70%
21-24 Years 25-28 Years 29-32 Years
24%
61%
15%
Age group
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TABLE II
Pearson Chi-Square=0.819 p=0.664
Majority of women who developed preeclampsia belong to age group of 25-28 years .However there was no statistical significance in development of preeclampsia with respect to age group.
Cross tab
DEVELOPED PE Total No Yes
age group
21-24 Years
Count 9 15 24
% within
DEVELOPED PE 20.5% 26.8% 24.0%
25-28 Years
Count 29 32 61
% within
DEVELOPED PE 65.9% 57.1% 61.0%
29-32 Years
Count 6 9 15
% within
DEVELOPED PE 13.6% 16.1% 15.0%
Total
Count 44 56 100
% within
DEVELOPED PE 100.0% 100.0% 100.0%
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TABLE III
ALPHA1_GROUP Total
0-1.86 ABOVE 1.86
age_group
21-24 Years
Count 9 15 24
% within
ALPHA1_GROUP 20.9% 26.3% 24.0%
25-28 Years
Count 29 32 61
% within
ALPHA1_GROUP 67.4% 56.1% 61.0%
29-32 Years
Count 5 10 15
% within
ALPHA1_GROUP 11.6% 17.5% 15.0%
Total
Count 43 57 100
% within
ALPHA1_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=1.381 p=0.501
TABLE IV Crosstab
FETAL_GROUP Total 0-1.92 ABOVE 1.92
age_group
21-24 Years
Count 9 15 24
% within
FETAL_GROUP 20.5% 26.8% 24.0%
25-28 Years
Count 29 32 61
% within
FETAL_GROUP 65.9% 57.1% 61.0%
29-32 Years
Count 6 9 15
% within
FETAL_GROUP 13.6% 16.1% 15.0%
Total
Count 44 56 100
% within
FETAL_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=0.819 p=0.664
There is no statistical significance between values of fetal hemoglobin and alpha 1 microglobulin with respect to age of pregnant women.
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TABLE V
PARITY Frequency Percent
Primi 56 56.0
Multi 44 44.0
Total 100 100.0
FIGURE II
56%
44%
PARITY
Primi Multi
50 Pearson ChiSquare=0.305 P=0.581
There were 53.6% primi and 46% multi in my study. Eventhough the incidence of preeclampsia was found to be more among primi, there was no statistical significance in parity with respect to preeclampsia.
TABLE VI
PARITY * DEVELOPED_PE Cross tabulation
DEVELOPED_PE Total
No Yes
PARITY
Primi
Count 26 30 56
% within
DEVELOPED_PE 59.1% 53.6% 56.0%
Multi
Count 18 26 44
% within
DEVELOPED_PE 40.9% 46.4% 44.0%
Total
Count 44 56 100
% within
DEVELOPED_PE 100.0% 100.0% 100.0%
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TABLE VII
BMI Group Frequency Percent
<18.5 16 16.0
18.5-24.99 67 67.0
25-29.99 11 11.0
ABOVE 30 6 6.0
Total 100 100.0
FIGURE III
0%
10%
20%
30%
40%
50%
60%
70%
<18.5 18.5-24.99 25-29.99 ABOVE 30
16%
67%
11%
6%
BMI Group
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TABLE VIII
Crosstab
DEVELOPED PE Total No Yes
BMI GROUP
<18.5
Count 7 9 16
% within DEVELOPED
PE 15.9% 16.1% 16.0%
18.5-24.99
Count 33 34 67
% within DEVELOPED
PE 75.0% 60.7% 67.0%
25-29.99
Count 4 7 11
% within DEVELOPED
PE 9.1% 12.5% 11.0%
ABOVE 30
Count 0 6 6
% within DEVELOPED
PE 0.0% 10.7% 6.0%
Total
Count 44 56 100
% within DEVELOPED
PE 100.0% 100.0% 100.0%
Pearson Chi-Square=7.969* p=0.047
Incidence of pre eclampsia was found to be more among BMI group of 18.5 to 24.99, there was no statistical significance between BMI and development of preeclampsia.
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TABLE IX
Crosstab
ALPHA1_GROUP Total 0-1.86 ABOVE
1.86
BMI_GROUP
<18.5
Count 7 9 16
% within
ALPHA1_GROUP 16.3% 15.8% 16.0%
18.5-24.99
Count 32 35 67
% within
ALPHA1_GROUP 74.4% 61.4% 67.0%
25-29.99
Count 4 7 11
% within
ALPHA1_GROUP 9.3% 12.3% 11.0%
ABOVE 30
Count 0 6 6
% within
ALPHA1_GROUP 0.0% 10.5% 6.0%
Total
Count 43 57 100
% within
ALPHA1_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=5.347 p=0.148
54
TABLE X
Crosstab
FETAL_GROUP Total 0-1.92 ABOVE
1.92
BMI_GROUP
<18.5
Count 6 10 16
% within
FETAL_GROUP 13.6% 17.9% 16.0%
18.5-24.99
Count 34 33 67
% within
FETAL_GROUP 77.3% 58.9% 67.0%
25-29.99
Count 4 7 11
% within
FETAL_GROUP 9.1% 12.5% 11.0%
ABOVE 30
Count 0 6 6
% within
FETAL_GROUP 0.0% 10.7% 6.0%
Total
Count 44 56 100
% within
FETAL_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=8.729 * p=0.033
There was no statistical significance between levels of fetal hemoglobin and alpha 1 microglobulin and BMI of pregnant women.
FIGURE IV
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Yes
No 16%
16%
61% 75%
13%
11% 9% 0%
ABOVE 30 25-29.99 18.5-24.99
<18.5
55
TABLE XI
FIGURE V
Out of hundred women, 56 women developed preeclampsia and 44 women did not develop preeclampsia.
44%
56%
DEVELOPED PE
NO YES
DEVELOPED PE Frequency Percent
No 44 44.0
Yes 56 56.0
Total 100 100.0
56
Blood pressure at admission
TABLE XII
BLOOD PRESSURE DEVELOPED PE DID NOT DEVELOP PE
SYSTOLIC(mm of Hg) 142 116.5
DIASTOLIC(mm of Hg) 96.8 75.7
MEAN ARTERIAL PRESSURE(mm of Hg)
111.33 89.3
FIGURE VI
The mean sysytolic, diastolic and mean arterial pressures of preeclamptic women were elevated at the time of admission. The mean arterial pressure was 89.3 mm of Hg in normotensive women and 111.33 mm of Hg in women who developed preeclampsia.
142
96.8 116.5 112
75.7
89.3
0 20 40 60 80 100 120 140 160
SYSTOLIC DIASTOLIC MEAN ARTERIAL PRESSURE DEVELOPED PE DID NOT DEVELOP PE
57
Usage of antihypertensives (TABLE XIII)
No of Antihypertensive drugs Preeclamptic women
NONE 12 (21.4%)
1 37 (66.1%)
2 7 (12.5%)
TOTAL 56 (100%)
In the antenatal period, all women with preeclampsia received antihypertensives for control of blood pressure. Among them, 49 required 1 antihypertensive drug and 7 required 2 antihypertensive drug.
FIGURE VII
No Of Antihypertensive Drugs
12
37
7
56
0 10 20 30 40 50 60
NONE 1 2 TOTAL
NO OF PREECLAMPTIC WOMEN
NO OF PREECLAMPTIC WOMEN
58
Type of labour (TABLE XIV)
ONSET OF LABOUR DEVELOPED PE NOT DEVELOPED
PREECLAMPSIA
SPONTANEOUS 3 28
INDUCTION 41 11
ELECIVE CAESEREAN 12 5
TOTAL 56 44
FIGURE VIII
The induction rate was higher in women who developed preeclampsia compared to women who did not develop pre eclampsia. Out of 56 women who had developed preeclampsia, labour was induced in 41, spontaneous onset of labour in 3 women and 12 underwent elective caesarean section.
3
41
12
56
28
11
5
44
0 10 20 30 40 50 60
SPONTANEOUS INDUCTION ELECTIVE LSCS TOTAL
DEVELOPED PE DID NOT DEVELOP PE
59
TABLE XV: MODE OF DELIVERY
MODE OF DELIVERY Frequency Percent
FTNVD 62 62.0
LSCS 38 38.0
Total 100 100.0
FIGURE IX
62%
38%
MODE OF DELIVERY
FTNVD LSCS
60
TABLE XIV
Crosstab
DEVELOPED PE Total No Yes
MODE OF DELIVERY
FTNVD
Count 33 29 62
% within DEVELOPED
PE 75.0% 51.8% 62.0%
LSCS
Count 11 27 38
% within DEVELOPED
PE 25.0% 48.2% 38.0%
Total
Count 44 56 100
% within DEVELOPED
PE 100.0% 100.0% 100.0%
Pearson Chi-Square=5.636* p=0.018
There was no statistical significance between mode of delivery and development of pre eclampsia.
MODE OF DELIVERY IN WOMEN WHO DEVELOPED PREECLAMPSIA
COUNT PERCENTAGE
FTNVD 29 51.8%
LSCS 27 48.2%
TOTAL 56 100%
Out of 56 women who developed preeclampsia,51% delivered by vaginal delivery and 48% delivered by LSCS which is not statistically significant
61
TABLE XVII
Crosstab
ALPHA1_GROUP Total 0-1.86 ABOVE
1.86
MODE OF DELIVERY
FTNVD
Count 32 30 62
% within
ALPHA1_GROUP 74.4% 52.6% 62.0%
LSCS
Count 11 27 38
% within
ALPHA1_GROUP 25.6% 47.4% 38.0%
Total
Count 43 57 100
% within
ALPHA1_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=4.938* p=0.026
TABLE XVIII
Crosstab
FETAL_GROUP Total 0-1.92 ABOVE
1.92
MODE OF DELIVERY
FTNVD
Count 33 29 62
% within
FETAL_GROUP 75.0% 51.8% 62.0%
LSCS
Count 11 27 38
% within
FETAL_GROUP 25.0% 48.2% 38.0%
Total
Count 44 56 100
% within
FETAL_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=5.636* p=0.018
There is no statistical significance between mode of delivery and values of fetal hemoglobin and alpha 1 microglobulin
62
TABLE XIX
Birth Weight Group Frequency Percent
<2.5 K.GMS 5 5.0
2.5-3.0 KGMS 57 57.0
ABOVE 3.0 KGMS 38 38.0
Total 100 100.0
FIGURE X
5%
57%
38%
Birth Weight Group
<2.5 K.GMS 2.5-3.0 KGMS ABOVE 3.0 KGMS
63
TABLE XX
Crosstab
DEVELOPED PE Total No Yes
birth weight group
<2.5 K.GMS
Count 3 2 5
% within DEVELOPED
PE 6.8% 3.6% 5.0%
2.5-3.0 KGMS
Count 21 36 57
% within DEVELOPED
PE 47.7% 64.3% 57.0%
ABOVE 3.0 KGMS
Count 20 18 38
% within DEVELOPED
PE 45.5% 32.1% 38.0%
Total
Count 44 56 100
% within DEVELOPED
PE 100.0% 100.0% 100.0%
Pearson Chi-Square=2.854 p=0.240
Birth weight of majority of babies (57%) were between 2.5 to 3.0 kgs.38% of babies were above 3.0 kgs and 5% of babies were less than 2.5 kgs.
64
TABLE XXI
Pearson Chi-Square=2.231 p=0.328
TABLE XXII
Crosstab
FETAL_GROUP Total 0-1.92 ABOVE
1.92
birth weight group
<2.5 K.GMS
Count 3 2 5
% within
FETAL_GROUP 6.8% 3.6% 5.0%
2.5-3.0 KGMS
Count 21 36 57
% within
FETAL_GROUP 47.7% 64.3% 57.0%
ABOVE 3.0 KGMS
Count 20 18 38
% within
FETAL_GROUP 45.5% 32.1% 38.0%
Total
Count 44 56 100
% within
FETAL_GROUP 100.0% 100.0% 100.0%
Pearson Chi-Square=2.854 p=0.240
There is no statistical significance between birth weight of babies and values of fetal hemoglobin and alpha 1 microglobulin
Crosstab
ALPHA1_GROUP Total 0-1.86 ABOVE
1.86
birth weight group
<2.5 K.GMS
Count 3 2 5
% within
ALPHA1_GROUP 7.0% 3.5% 5.0%
2.5-3.0 KGMS
Count 21 36 57
% within
ALPHA1_GROUP 48.8% 63.2% 57.0%
ABOVE 3.0 KGMS
Count 19 19 38
% within
ALPHA1_GROUP 44.2% 33.3% 38.0%
Total
Count 43 57 100
% within
ALPHA1_GROUP 100.0% 100.0% 100.0%
65
FIGURE XI: GESTATIONAL AGE OF DELIVERY
Most of the women who developed preeclampsia delivered around 37 weeks. This is due to the higher induction rate in these women
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Yes
No 52%
2%
41%
9%
7%
52%
0%
36%
40 Weeks 39 Weeks 38 Weeks 37 Weeks
66
FIGURE XII
TABLE XXIII
GA_OF_DELIVERY * DEVELOPED_PE Crosstabulation
DEVELOPED_PE Total No Yes
GA_OF DELIVERY
37.00 Count 1 29 30
% within DEVELOPED_PE 2.3% 51.8% 30.0%
38.00 Count 4 23 27
% within DEVELOPED_PE 9.1% 41.1% 27.0%
39.00 Count 23 4 27
% within DEVELOPED_PE 52.3% 7.1% 27.0%
40.00 Count 16 0 16
% within DEVELOPED_PE 36.4% 0.0% 16.0%
Total Count 44 56 100
% within DEVELOPED_PE 100.0% 100.0% 100.0%
Pearson Chi-Square=68.419** P<0.001
51.8% of women who developed preeclampsia delivered around 37 weeks of gestation which is statistically significant
36.50 37.00 37.50 38.00 38.50 39.00 39.50
PE NO PE YES
39.23
37.55
COMPARISON OF GA OF DELIVERY FOR PRE ECLAMPSIA
67
COMPARISON OF INTERVAL SCALING VARIABLES LIKE AGE, BMI, WEEKS OF GA, FETAL, ALPHA1, GA OF
DELIVERY, BIRTH WEIGHT (TABLE XX1V)
Independent Samples Test
DEVELOPED PE N Mean Std.
Deviation
Std.
Error Mean
T VALUE
P VALUE
AGE No 44 26.227 2.208 0.333 0.231 0.818
Yes 56 26.339 2.546 0.340
BMI No 44 21.215 3.343 0.504 1.437 0.154
Yes 56 22.593 5.629 0.752
WEEKS OF GA No 44 12.977 1.320 0.199 0.171 0.865 Yes 56 13.018 1.053 0.141
ALPHA 1
MICROGLOBULIN
No 44 1.490 0.183 0.028 17.788** P<0.001 Yes 56 2.446 0.317 0.042
FETAL
HEMOGLOBIN
No 44 0.994 0.489 0.074 22.928** P<0.001 Yes 56 3.219 0.476 0.064
GA OF DELIVERY No 44 39.227 0.711 0.107 12.460** P<0.001 Yes 56 37.554 0.630 0.084
BIRTH WEIGHT No 44 2.950 0.280 0.042 1.301 0.196 Yes 56 2.882 0.241 0.032
**P<0.001
68 DESCRIPTIVE FOR INTERVAL SCALING (TABLE XXV)
Statistic
Mean
95%
Confidence Interval for
Mean
Median
Std.
Deviation Minimum Maximum Lower
Bound
Upper Bound
Age 26.290 25.815 26.765 26.000 2.392 22.00 32.00 BMI 21.987 21.036 22.937 21.295 4.789 12.90 45.81 Weeks of GA 13.000 12.767 13.233 13.000 1.172 11.00 16.00 Alpha 1
microglobulin
2.025 1.917 2.133 2.095 0.546 1.04 3.20 Fetal
hemoglobin
2.240 2.000 2.480 2.580 1.209 .28 3.66 GA of delivery 38.290 38.078 38.502 38.000 1.066 37.00 40.00 Birth weight 2.912 2.860 2.964 2.900 0.260 2.40 3.50
The mean age of the women in the study was 26.22. The mean age of women who developed preeclampsia was 26.3±2.2 years.
Mean BMI of women who developed preeclampsia was 22.5±5.6.
Mean BMI of normal pregnant women was 21.2±3.3.
And mean gestational age of delivery was 37.5±0.6 weeks.
69
FIGURE XIII
TABLE XXVI
Crosstab
DEVELOPED PE Total No Yes
ALPHA 1 GROUP
0-1.86
Count 43 0 43
% within DEVELOPED
PE 97.7% 0.0% 43.0%
ABOVE 1.86
Count 1 56 57
% within DEVELOPED
PE 2.3% 100.0% 57.0%
Total
Count 44 56 100
% within DEVELOPED
PE 100.0% 100.0% 100.0%
Pearson Chi-Square=96.013** P<0.0001
There exists a statistical significance between the high levels of alpha 1 microglobulin and development of preeclampsia
0.00 0.50 1.00 1.50 2.00 2.50
PE NO PE YES
1.49
2.45
COMPARISON OF ALPHA 1 MICROGLOBULIN FOR PRE ECLAMPSIA
70
FIGURE XIV
Sensitivity of alpha 1 microglobulin is 100% and specificity is 23%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 - 1.86 Above 1.86
0%
100%
98%
2%
NO YES
71
FIGURE XV
TABLE XXVII
DEVELOPED PE Total No Yes
FETAL GROUP
0-1.92
Count 43 1 44
% within DEVELOPED
PE 97.7% 1.8% 44.0%
ABOVE 1.92
Count 1 55 56
% within DEVELOPED
PE 2.3% 98.2% 56.0%
Total
Count 44 56 100
% within DEVELOPED
PE 100.0% 100.0% 100.0%
Pearson Chi-Square=92.048** P<0.0001
Sensitivity of fetal hemoglobin is 98.2% and specificity is 23%
0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50
PE NO PE YES
0.99
3.22
COMPARISON OF FETAL HEMOGLOBIN FOR PRE ECLAMPSIA
72
TABLE XXVIII
ALPHA2_GROUP * FETAL_GROUP Cross Tabulation
FETAL_GROUP Total 0-1.92 ABOVE
1.92
ALPHA1 GROUP
0-1.86
Count 42 1 43
% within
FETAL_GROUP 95.5% 1.8% 43.0%
ABOVE 1.86
Count 2 55 57
% within
FETAL_GROUP 4.5% 98.2% 57.0%
Total
Count 44 56 100
% within
FETAL_GROUP 100.0% 100.0% 100.0%
Mcnemar p>0.05 so sensitivity was difference between two test
73
TO FIND OUT THE CUTOFF VALUES FOR ALPHA 1 AND FETAL HB WE USED ROC CURVE
TABLE XXIX
Test Result Variable(s) Area Std.
Errora
Asymptotic Sig.b Asymptotic 95% Confidence Interval
Lower Bound Upper Bound ALPHA 1
MICROGLOBULIN 1.000 .000 .000 1.000 1.000
FETALHEMOGLOBIN .998 .003 .000 .992 1.000
a. Under the nonparametric assumption b. Null hypothesis: true area = 0.5
1